Olefin metathesis in the ionic liquid 1-butyl-3-methylimidazolium hexafiuorophosphate using a recyclable Ru catalyst: Remarkable effect of a designer ionic tag

Article abstract of DOI:10.1002/anie.200351222

Designer labels: Ruthenium carbene complex 1 bearing an ionic tag was shown to be a highly reactive catalyst for the ring-closing metathesis of various diene and enyne substrates in minimally ionic solvent systems (see scheme; Bmim = 1-butyl-3-methylimida

Full text of DOI:10.1002/anie.200351222

Angewandte
Chemie
themes of contemporary synthetic chemistry.[1] In this context,
efficient recycling and subsequent reuse of homogeneous
catalysts are of prime importance.[2] The recently emerged
room-temperature ionic liquids hold great potential in meet-
ing these demands, as evidenced by their increasing popular-
ity as innovative and environmentally benign reaction media
as well as their use as new vehicles for the immobilization of
transition-metal-based catalysts.[3]
The spectacular recent success of olefin metathesis[4]
catalyzed by metal–carbene complexes stems largely from
the availability of several well-defined catalysts, most notably,
the Grubbs-type ruthenium alkylidenes 1[5] and 2.[6] Another
major advance in this area is the discovery by Hoveyda and
co-workers[7] of the recyclable Ru catalysts 3 (Cy = cyclohex-
yl) and 4 (Mes = mesityl = 2,4,6-trimethylphenyl). We[8] and
other research groups[9] have established that various poly-
meric and solid supports can be used to immobilize these
catalysts, as exemplified by the poly(ethylene glycol)-bound
catalyst 5 (PEG = poly(ethylene glycol)). Herein, we report
Olefin Metathesis in Ionic Liquids
our success in the development of Ru complex 6 that features
a designer ionic tag incorporated in catalyst 3. This catalyst
can be repeatedly recycled and reused as a highly active
catalyst for the ring-closing metathesis (RCM) of various
diene and enyne substrates in a minimally ionic solvent
system (1-butyl-3-methylimidazolium hexafluorophosphate
([Bmim]PF6)[10]/CH2Cl2, 1:9 v/v) without significant loss of
its activity.
Olefin Metathesis in the Ionic Liquid 1-Butyl-3-
methylimidazolium Hexafluorophosphate Using a
Recyclable Ru Catalyst: Remarkable Effect of a
Designer Ionic Tag**
Qingwei Yao* and Yiliang Zhang
Several Ru carbene complexes, including 1 and 2, have
been shown to be catalytically active for olefin metathesis in
room-temperature ionic liquids, but their catalytic reactivity
rapidly vanished in subsequent recycling runs and reuse.[11]
We suspected that the rapid deactivation of the Ru catalysts
might have been caused by the highly ionic nature of the
solvents used, and we elected to re-examine the behavior of
catalysts 1 and 3 in the RCM of the test diene 7 (Ts = toluene-
4-sulfonyl) using a mixture of the ionic liquid [Bmim]PF6 and
CH2Cl2 (1:9 v/v) as the solvent (Table 1). Although the RCM
of 7 proceeded uneventfully in the first run, as indicted by the
clean and quantitative formation of the cyclized product 8
with either 1 or 3, subsequent reuse of the catalysts recovered
from the ionic liquid layer[12] resulted in a dramatic decrease
in the conversion of 7. While the poor recyclability of catalyst
Environmental concern associated with chemical synthesis
has posed stringent and compeling demands for greener
processes, and the development of cost-effective and environ-
mentally benign catalytic systems has become one of the main
[*] Prof. Dr. Q. Yao, Y. Zhang
Department of Chemistry and Biochemistry
The Michael Faraday Laboratories
Northern Illinois University
DeKalb, IL 60115-2862 (USA)
Fax: (+1)815-753-4802
E-mail: qyao@niu.edu
[**] This work was supported by grants from the National Institutes of
Health (GM63522) and the Petroleum Research Fund, administered
by the American Chemical Society (36466-G1).
Angew. Chem. Int. Ed. 2003, 42, 3395 – 3398
DOI: 10.1002/anie.200351222
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3395

Communications
Table 1: Recycling and reuse of Ru catalysts 1 and 3 in the ring-closing
which was previously used in the synthesis of PEG-bound
catalyst 5. Alkylation of 9 with 1-chloro-4-iodobutane under
standard conditions gave chloride 10. Reaction of 10 with
imidazole in the presence of NaH yielded 11 which was
subsequently methylated with iodomethane to give the
imidazolium iodide 12. Anion exchange of iodide 12 with
AgPF6 furnished the imidazolium hexafluorophosphate
13.[14,15] Treatment of 13 with the Grubbs catalyst 1 (first
with 1.0 equiv of 1 followed by a second portion of 0.5 equiv
of 1) in the presence of CuCl in CH2Cl2 at 508C, as described
by Hoveyda and co-workers,[7b] resulted in complete exchange
of the styrene group to deliver the air-stable brownish powder
6,[16] which was fully characterized by 1H and 13C NMR
spectroscopy as well as by elemental analysis.
metathesis of diene 7.[a]
Catalyst 1
Catalyst 3
Cycle
1
2
3
1
2
3
reaction time [h]
3
>98
3
54
6
41
3
>98
3
75
6
37
conversion [%][b]
[a] All reactions were performed with 0.5 mmol of the substrate in the
solvent system [Bmim]PF6/CH2Cl2 (1:9 v/v, 10 mL) at 508C under an Ar
atmosphere. [b] Determined by 1H NMR spectroscopy at 500 MHz.
Catalyst 6 was then evaluated for its performance toward
the RCM of diene 7 under the same conditions as used for
catalysts 1 and 3. As shown in Table 2, this simple ligand
modification resulted in a vast improvement over both
catalysts 1 and 3. Catalyst 6 can be recycled and reused at
1 could be attributed to its known liability toward decom-
position, failure to efficiently recover the more robust catalyst
3 indeed pointed to a limitation in using [Bmim]PF6 as an
effective means to immobilize Ru catalysts.[13]
It became apparent that an
enhancement in the partitioning of
Table 2: Recycling and reuse of Ru catalyst 6 in the ring-closing metathesis of diene 7.[a]
the Ru catalyst in the ionic liquid
would ultimately be required. We
further reasoned that incorporation
of an ionic tag mirroring the struc-
tural motif of the ionic liquid would
best meet such a requirement. To
this end, ligand 13 was designed,
and synthesized as shown in
Scheme 1. The preparation of 13
commenced from the hydroxy-func-
Cycle
1
2
3
4
5
6
7
8
9
10
90
conversion [%][b]
>98
>98
97
96
95
94
92
92
91
[a] The reactions were performed with 0.5 mmol of the substrate in the solvent system [Bmim]PF6/
1
CH2Cl2 (1:9 v/v, 10 mL) at 508C under an Ar atmosphere. [b] Determined by H NMR spectroscopy at
tionalized isopropoxystyrene 9,[8] 500 MHz .
least 10 times with only a very slight decrease in reactivity
after each run. It should be noted that the recycling of both
the catalyst and the ionic liquid can simply be carried out in
the air by first removing the more volatile CH2Cl2 under
vacuum followed by extraction of the product with diethyl
ether.
Having established the superior recyclability and re-
usability of 6, we next examined a variety of other represen-
tative RCM substrates that lead to the formation of various
carbocyclic as well as nitrogen-, oxygen-, and sulfur-contain-
ing heterocyclic compounds (Table 3). The benchmark diene
substrate toluenesulfonamide 14 cyclized cleanly with high
conversion under conditions similar to those used for the
metathesis of 7 (entries 1 and 2). Use of a reduced amount
(2.5 mol%) of the catalyst relative to the substrate also led to
high conversion, even at room temperature (entry 3). The
recycled catalyst/ionic liquid from the reaction of 14 was
subsequently used for the metathesis of a second substrate
(16; entry 4). The crude reaction product from 16 consists of
only the cyclized product 17 and recovered 16 devoid of any
detectable amount of the product from the previous reaction,
thus demonstrating the practical advantage of the sequential
use of a recyclable and reusable catalyst. Similarly, another
batch of catalyst 6 was used to catalyze the RCM of diene 18
Scheme 1. Preparation of Ru carbene complex 6.
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Table 3: Ring-closing metathesis catalyzed by Ru complex 6 in [Bmim]PF6/CH2Cl2.[a]
to the immobilization of other tran-
sition-metal-based catalysts. Appli-
cation of the phase-tagging ligand
13 to the immobilization of the
more-powerful second-generation
Entry
Substrate (conc)
Product
Catalyst [mol%]
Conditions
Conversion [%][b]
(yield [%][c])
1
(0.05m)
(0.05m)
(0.1m)
5
5
2.5
508C, 3 h
508C, 3 h
RT, 12 h
98(95)
97(94)
>98(96)
Grubbs catalyst
2 is currently
2
3[d]
underway in our laboratory.
Experimental Section
4[d]
2.5
508C, 4 h
95(89)
Ring-closing metathesis of diene 7 and
general procedure for the recycling and
reuse of Ru catalyst 6 and ionic liquid
[Bmim]PF6: A 25-mL oven-dried round-
bottom flask equipped with a reflux
condenser was charged with 6 (22.4 mg,
0.025 mmol). The flask was evacuated
and filled with Ar. The ionic liquid
[Bmim]PF6 (1 mL) was then added and
the flask was degassed 3 times by first
evacuation and then filling with Ar.
Diene 7 (140 mg, 0.50 mmol) was then
added in anhydrous CH2Cl2 (9 mL). The
flask was then heated to gentle reflux
(bath temperature 45–508C) for 3 h.
After cooling the reaction mixture to
room temperature, it was concentrated
under vacuum to remove the cosolvent
CH2Cl2 and extracted with anhydrous
diethyl ether (3 ” 5 mL). The combined
ether extracts were evaporated to give
125 mg of a crude reaction product.
Examination of this crude reaction mix-
ture by 500 MHz 1H NMR spectroscopy
revealed complete conversion of 7 and
the clean formation of the cyclized
product 8. The ionic layer was dried on
the vacuum line prior to its reuse in a
subsequent run as described below.
1
2
(0.05m)
(0.05m)
5
5
508C, 3 h
508C, 3 h
98(90)
96(89)
3[g]
(0.02m)
(0.05m)
(0.05m)
5
5
5
508C, 6 h
508C, 6 h
508C, 4 h
92(70)
78(72)
87(83)
4
5
[a] Unless otherwise indicated, all reactions were performed under the following standard conditions:
0.5 mmol of substrate in the solvent system [Bmim]PF6/CH2Cl2 (1:9 v/v, 10 mL) under an Ar atmosphere
at the indicated temperature. [b] Determined by H NMR spectroscopy at 500 MHz. [c] Yield of pure
product after chromatography on silica gel. [d] Performed with 1.0 mmol of substrate. [e] Ref. [8].
[f] Ref. [17]. [g] Performed with 0.5 mmol of substrate in the solvent system [Bmim]PF6/CH2Cl2 (1:24 v/v,
25 mL). Bz=benzyl.
1
A second run of the metathesis of 7
using the recycled catalyst and ionic
liquid was conducted in exactly the same
way as described for the first cycle, and
resulted in the clean formation of 8 and complete conversion of 7.
This reaction was repeated eight more times, each time using the
catalyst and ionic liquid recovered from a previous cycle. The results
are listed in Table 2.
to deliver the dihydropyran 19 for two runs with essentially
equal efficacy. The recovered catalyst was then reused
consecutively in the RCM of another three different sub-
strates, each giving high yields of the respective product,
without any replenishment of either the catalyst or the ionic
liquid. It is noteworthy that the catalyst remained highly
active (entry 5) even after being recovered from an enyne
metathesis (entry 4),[17] which generates a hindered and
stabilized Ru–vinylalkylidene intermediate rather than the
more reactive Ru–methylidene species as in the case of the
RCM of terminal dienes. Catalyst regeneration from the
former intermediate would be expected to be more diffi-
cult.[18,19]
In conclusion, we have presented evidence that a task-
specific modification of the bidentate ligand in 3 brings about
an immense improvement in its performance as a recyclable
catalyst for olefin metathesis in an ionic liquid. Given the
ever-growing interest in the development of catalytic systems
suitable for organic synthesis in ionic liquids, the phase-
tagging strategy described here could, in principle, be applied
Received: February 19, 2003
Revised: May 12, 2003 [Z51222]
Keywords: carbene complexes · homogeneous catalysis ·
.
ionic liquids · metathesis · ruthenium
[1] For selected recent reviews and monographs on green chemistry,
see a) “Green Chemistry: Designing Chemistry for the Environ-
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Angew. Chem. Int. Ed. 2003, 42, 3395 – 3398
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Communications
Wiley-VCH, Weiheim, 1996, chap. 3.1; b) Chiral Catalyst Immo-
The ionic liquid layer can be readily separated from the reaction
mixture by removing the cosolvent CH2Cl2 under vacuum first,
followed by extraction of the product and any starting material
with diethyl ether.
bilization and Recycling (Eds.: D. E. De Vos, I. F. J. Vankelecom,
P. A. Jacobs), Wiley-VCH, Weiheim, 2000; c) N. E. Leadbeater,
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[13] While the poor recyclability of 3 could be attributed in part to
the deactivation of the catalytically active Ru–methylidene
intermediate formed in the initial turnover, we believe that the
diminished activity of the recovered catalyst in the ionic liquid
layer is largely due to the extraction of 3 into the diethyl ether
layer. To probe this possibility, a solution of N-tosyldiallylamine
in [Bmim]PF6/CH2Cl2 (1:9 v/v, 0.05m) was treated with 5 mol%
of 3 at 508C for 2h. After separation of the crude reaction
product from the ionic liquid layer, 1H NMR analysis revealed a
complete conversion of the diene and the presence of catalyst 3
(as evidenced by its carbene signal at d = 17.4 ppm) in the crude
reaction mixture. The crude reaction mixture was then dissolved
in CH2Cl2 and recharged with another portion of the diene. After
heating the reaction mixture to reflux for 2h, it was analyzed by
1H NMR spectroscopy, which indicated a 98% conversion of the
diene. A similar reaction was performed using the recovered
ionic liquid. Only 22% of the added diene was found to be
converted into the cyclized product.
[3] Selected recent reviews on ionic liquids and their application in
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[6] a) M. Scholl, S. Ding, C. W. Lee, R. H. Grubbs, Org. Lett. 1999, 1,
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Morgan, R. H. Grubbs, Tetrahedron Lett. 1999, 40, 2 2 47; c) J.
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[14] NMR data of 13: 1H NMR (500 MHz, CDCl3): d = 8.48 (s, 1H),
7.24 (d, J = 17.5 Hz, 2H), 7.03–6.98 (m, 2H), 6.82(d, J = 8.8 Hz,
1H), 6.73 (dd, J = 3.2, 8.8 Hz, 1H), 5.72 (d, J = 17.9 Hz, 1H), 5.24
(d, J = 11.4 Hz, 1H), 4.37 (hept, J = 6.1 Hz, 1H), 4.20 (t, J =
7.4 Hz, 2H), 3.94 (t, J = 5.9 Hz, 2H), 3.85 (s, 3H), 2.05 (quint,
J = 7.4 Hz, 2H), 1.74–1.80 (m, 2H), 1.30 ppm (d, J = 6.1 Hz,
6H); 13C NMR (125 MHz, CDCl3): d = 152.9, 149.6, 136.0, 131.6,
129.2, 123.5, 122.0, 117.1, 114.8, 114.4, 111.9, 72.3, 67.4, 49.8, 36.2,
27.0, 25.8, 22.2 ppm.
[15] The presence of free iodide in the reaction media may adversely
effect the activity of Grubbs-type Ru catalysts as a result of
potential ligand exchange, see a) E. L. Dias, S. T. Nguyen, R. H.
Grubbs, J. Am. Chem. Soc. 1997, 119, 3887; b) M. S. Sanford,
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1
[16] Data of 6: H NMR (500 MHz, [D6]acetone): d = 17.37 (d, J =
5.2Hz, 1H), 9.06 (s, 1H), 7.83 (s, 1H), 7.73 (s, 1H), 7.42(d, J =
2.7 Hz, 2H), 7.30 (dd, J = 2.8, 9.1 Hz, 1H), 7.24 (d, J = 9.1 Hz,
1H), 5.30 (hept, J = 6.0 Hz, 1H), 4.51 (t, J = 7.3 Hz, 2H), 4.13 (t,
J = 6.0 Hz, 2H), 4.07 (s, 3H), 2.41 (m, 3H), 2.22–1.26 (m, 34H),
1.75 ppm (d, J = 6.2Hz, 6H); 13C NMR (125 MHz, [D6]acetone):
d = 154.5, 147.1, 144.2, 137.0, 124.0, 122.6, 115.4, 113.8, 107.3,
75.2, 67.8, 49.5, 36.0, 35.4 (d, JCP = 25.3 Hz), 29.8, 27.5 (d, JCP
=
10.1 Hz), 27.0, 26.1, 25.7, 21.5 ppm; elemental analysis (%) calcd
for C36H58Cl2F6N2O2P2Ru: C 48.11, H 6.50, N 3.12; found: C
48.09, H 6.45, N 3.05.
[17] Q. Yao, Org. Lett. 2002, 4, 428.
[18] Q. Yao, Org. Lett. 2001, 3, 2069.
[19] M. Mori, N. Sakakibara, A. Kinoshita, J. Org. Chem. 1998, 63,
6082.
[10] [Bmim]PF6 can either be purchased from Acros Organics at a
relatively low cost or readily made in large quantities by simple
procedures.
[11] a) R. C. Buijsman, E. van Vuuren, J. G. Sterrenburg, Org. Lett.
2001, 3, 3785; b) D. Semeril, H. Olivier-Bourbigou, C. Bruneau,
P. H. Dixneuf, Chem. Commun. 2002, 146; c) K. G. Mayo, E. H.
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[12] [Bmim]PF6 is essentially nonvolatile and almost completely
insoluble in nonpolar solvents such as hexane and diethyl ether.
3398
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